Index

The Survival of "Global Health" - Part Seven: Patents and Potential Pandemics

I wouldn’t want to be Dr. Ali
Zaki right now. The Egyptian physician/scientist is in the center of a
maelstrom that unfolded this week in Geneva, Switzerland at the sixty-sixth
session of the World Health Assembly. And if history applies to this latest
brouhaha in the ongoing MERS-CoV SARS-like virus outbreak mess, Zaki was wise
to abandon his job at Dr. Soliman Fakeeh Hospital in Jeddah, leave Saudi Arabia,
and ply his trade in Cairo.

Saudi Arabia's Deputy
Health Minister Ziad Memish

Saudi Arabia's Deputy Health Minister Ziad Memish told the World Health
Organization meeting that “someone” – a reference to Zaki – mailed a sample of
the new SARS-like virus out of his country in June 2012, and gave it to Dutch
virologist Ron Fouchier of Erasmus University in Rotterdam. And Fouchier “patented
it.”"The virus was sent out of the country and it was patented, contracts
were signed with vaccine companies and anti-viral drug companies and that's why
they have a MTA (Material Transfer Agreement) to be signed by anybody who can
utilize that virus and that should not happen," Memish charged
in a speech at the World Health Assembly.

Memish claimed that the Saudi
government’s failure to share samples of the MERS-nCoV virus with other
countries – including neighbor states that had their own cases of the disease –
stemmed directly from Zaki’s actions. Though Memish referred to a “patent” in
his remarks to the Assembly, the Dutch team has not patented the viral genetic
sequence, but has placed it under a Material Transfer Agreement, or MTA,
requiring sample recipients to contractually agree not to develop products or
share the sample without the permission of Erasmus University and the Fouchier
laboratory. Memish’s comments were a bit confusing, but he seems to be saying
that Saudi Arabia refused to sign an MTA with a foreign government for a virus
that originated inside Saudi Arabia and has taken its greatest toll on the
Saudi people.

As of today
44 cases of MERS-CoV have been confirmed, 33 of them in Saudi Arabia, largely
in the country’s eastern date palm agricultural area. Worldwide, the virus has
caused cases in seven countries, and killed 22 people. MERS-CoV (“Middle
Eastern Respiratory Syndrome coronavirus”) is part of a class of viruses for
which there are no effective cures or vaccines. Like its close cousin the SARS
virus, MERS ravages the lungs of infected people, causing pneumonia and acute
respiratory distress. Also like SARS, it is previously unknown to human immune
systems, so reaction to infection can include the classic “cytokine storm”
reaction of an over-responsive immune system that hits the virus with all its
got, creating collateral damage all over the body. But unlike SARS – worse – it
also attacks the kidneys, causing renal failure.

Epidemiologically, MERS seems to
be quite similar to SARS, as it is easily spread by close contact, and can be
airborne transmitted between people. Both viruses are dangerous for healthcare
workers, and easily spread within hospitals. (WHO insists SARS was considerably more threatening for nosocomial transmission than MERS has been.) There is no rapid diagnostic test
for MERS, which puts doctors and nurses at special risk as they cannot easily
discriminate the symptoms differences between early stage MERS-CoV patients and
regular pneumonia. The MERS cases should be handled with maximum quarantine and
protective gear, which the routine pneumonia case rarely poses a risk for the
healthcare worker or other hospital patients. But there is no easy way to
recognize which is the case in any given patient. Until a rapid diagnostic is
developed, anxiety among healthcare workers in affected areas will remain high.

Memish charged this week that the
lack of a reliable diagnostic test for MERS was directly due to the “patents”
taken out by the Dutch. In the absence of such a test (with only PCR DNA assays
to work with)), "We think contact isolation needs to be applied, because
some patients present with diarrhea or vomiting, which we think could be the
source of the transmission," Memish said, noting that such procedures are
costly and trying psychologically for both patients and medical staff. The WHO endorses
this high level of hospital caution.

"There was a lag of three months
where we were not aware of the discovery of the virus," Memish told
the WHO meeting.Zaki sent his samples to Rotterdam in
June 2012; Fouchier, Zaki, and others co-authored an analysis that appeared in
the November 2012 issue of the New England Journal
of Medicine.

WHO Director-General Margaret
Chan listened carefully to simultaneous translation of Memish’s remarks, and
then lashed out.

"Making deals between
scientists because they want to take IP (intellectual property), because they
want to be the world's first to publish in scientific journals, these are
issues we need to address. No IP will stand in the way of public health
actions," Chan stated.
She exhorted
the Assembly delegates to "share your specimens with WHO collaborating
centers, not in a bilateral manner. Please, I'm very strong on this point, and
I want you to excuse me. Tell your scientists in your country, because you're
the boss. You're the national authority. Why would your scientists send
specimens out to other laboratories on a bilateral manner and allow other
people to take intellectual property rights on a new disease?"

The new MERS-CoV is shrouded in mystery right now, as
Saudi investigators have been unable to determine its reservoir species – where
did it come from – how it is spread from that species to people, a method for
rapid diagnosis, proper treatment and best approaches to hospital infection
control.Suspicions point to fruit bats in the
eastern Al-Ahsa province of Saudi Arabia, where the bulk of the cases have
occurred. Like the Nipah virus in Southeast Asia, a model is suggested, but not
proven, in which people working in the date tree harvests are exposed to the
virus as it is passed from date-eating bats. Bats tend to take fruit into their
mouths, chew it until they reach the pits, and then spit the pits out. The
virus may be passed in bat saliva that coats the chewed, regurgitated fruit
parts.

But that is at this point
speculation.

"We have a high level of
concern over the potential... for this virus to have sustainable
person-to-person spread," WHO deputy chief Keiji Fukuda told
the Assembly. Fukuda concurred with Memish’s assessment telling
reporters that WHO “is struggling with diagnostics" because of the Dutch
Material Transfer Agreement.

In March, before this controversy
exploded, Zaki shared his side of the story with The
Guardian. Eleven months ago, Zaki said, he was called in as a
consultant on a mysterious case in his hospital. Using his skills as a
virologist, Zaki tried to identify the virus, but the patient died less than 24
hours after he received the sample.Soon,
a second case came his way, and Zaki knew that he needed help. So last June he
mailed a sample to his friendRon
Fouchier. Three months later Zaki sent a notice in September 2012 to ProMED, a
disease alert system run by the Infectious Diseases Society of America. Under
pressure from the Saudi government, Zaki’s hospital fired him when the ProMED
notice was posted, and he eventually moved to Cairo.

A new human coronavirus was isolated from a patient with pneumonia by
Dr Ali Mohamed Zaki at the Virology Laboratory of Dr Soliman Fakeeh
Hospital Jeddah Saudi Arabia.

The virus was isolated from sputum of a male patient aged 60 years old
presenting with pneumonia associated with acute renal failure. The
virus grows readily on Vero cells and LLC-MK2 cells producing CPE in
the form of rounding and syncetia formation.

Meanwhile, contrary to
Memish’s depiction this week in the World Health Assembly, the general recognition of the
existence of this new disease was not prompted by a Fouchier/Zaki research
paper, but by the case of a Qatari man who, after visiting Saudi Arabia, flew
to London and came down with acute respiratory distress and kidney failure.
Physicians at St. Thomas’s Hospital saw Zaki’s ProMED posting, noted the
patient had traveled in Saudi Arabia, and concluded they were dealing with a
new virus. The London team isolated a viral sample, and compared it to the
genetic sequence Fouchier had prepared of Zaki’s sample – they were a match. UK
authorities went public with the news, spawning the first tier of worldwide
attention to the existence of a new human virus.

In March, Fouchier told The
Guardian that “very little is being done to
find out,” how and where the virus was circulating in the Middle East. He
hinted at lack of response from Saudi authorities, concluding that it was up to
Europe to learn all it could, and create systems to protect its peoples. (Fouchier's claim that "very little is being done" is untrue, according to sources that decline to be named because of delicate working relations with the Saudi government: They insist detailed study of the resevoir/animal host issue, as well as human epidemiology, is underway and will soon be released.)

The situation in the Middle East
is, indeed, dicey. Though the wars and conflicts of Syria and Iraq have not
reached bucolic Al-Ahasa, Saudi Arabia has many reasons to keep such outbreaks
quiet. Chief among them is the country’s role as the home of Islam, and host of
the Haj to Mecca. Concern about spread of disease during the annual Haj, which
is attended by Moslems from every corner of the planet, has been a constant
since the 14th century, when that Black Death exploded across Arabia and spread
via infected religious pilgrims across the Islamic world.

Several research teams from the United
States and Europe have offered their services to the Saudis since September,
but the situation is extremely complicated. The Saudi Kingdom is a Wahabi Sunni
state, but the affected region includes a large Shi’a population. Tensions
throughout the Middle East make free movement of Western – especially American –
scientists dangerous, and impossible if they are government officials. In this
situation academic scientists such as Dr. Allison McGeer of Toronto's Mt. Sinai Hospital or Columbia University’s Ian Lipkin have
more possibility of investigating the ground situation than do government
epidemiologists from the United States or European Centers for Disease Control.

Which takes us back to this
patent, or MTA dispute.

Memish only yesterdayagreedto
send samples of the virus to the U.S. CDC for analysis, in hopes of identifying
the animal reservoir for the disease. Presumably he has had these samples for
some time, and could have passed them on months ago. It is not clear why a
Dutch MTA related to the genetic sequence of a virus could have prevented open
sharing of these samples months ago. (We are aware of an arrangement under which samples have been shared from Memish's office to a foreign lab, and data may soon be released. The arrangement is not public at this time, and the research is not completed.)

In contrast, China shared H7N9 flu
sequences with open source Internet sites within four weeks of the first
patient cases in Shanghai, and sent viral samples all over the world within
less than two months. Canada’s National Microbiology Laboratory
Director Francis Plummer told
the CBC in mid-May that his Winnipeg lab had signed the Dutch MTA, and
obtained a research sample, after prolonged legal negotiations. Plummer
contrasted his difficulties in obtaining a sample from the Dutch to China’s
immediate and open sharing of H7N9 influenza samples with his facility.

In a carefully craftedpress releaseyesterday Erasmus Medical Center
spelled out the terms and understandings of its original MTA “patent” (I put
“patent” in quotation marks because an MTA is not a patent at all, but media accounts, Memish
and Saudi officials have framed it as such). It states unequivocally, “Erasmus
MC was the first to identify the new coronavirus (MERS coronavirus).” The press release continues:

“It is clear that all research institutions worldwide that
want to carry out such research will receive the virus free of charge from
Erasmus MC. Indeed many research institutions already received the virus
together with additional materials and information from Erasmus MC. For
shipment of the virus it is mandatory that a material transfer agreement (MTA)
is signed by the recipient institution, as is common practice when shipping
viruses. Such an MTA covers issues like liability and limitations to commercial
use. Consequently the virus may not yet be used for commercial purposes and may
not be distributed to third parties without permission. These are the usual
conditions covered by a MTA.

“MTAs were implemented to facilitate scientific research as
well as exchange of materials to the benefit of public health. Ab Osterhaus and
Ron Fouchier of Erasmus MC stress that ‘every research or public health
laboratory that complies with the safety criteria for handling MERS coronavirus
can work with it’.

“It is clearly a misunderstanding that Erasmus MC owns the virus. Only specific
applications related to it, like vaccines and medicines can be patented.”

In an interview withBloomberg
Businessweekthe Dutch researchers insisted that they are freely sharing
their samples, and there are no patent disputes on the table.

This is not likely to placate the new World Health Assembly
wrath. Chan called upon the gathered delegates to stand against intellectual
property blocks to epidemic responses and the crowd cheered. The question of
ownership of discovery has become The Number One wedge issue in global health
today, underscoring debate on everything frompharmaceutical
safety/counterfeitingto
availability of antibiotics for TB care.

Chan and WHO are especially sensitive to the issue because
of the 2007-08 battle between the agency and the Indonesian government
regarding the H5N1 flu virus and then-Minister of Health Siti Supari’s
insistence on the existence of "viral sovereignty." Supari declined to
share samples of the dangerous bird flu viruses that were then rampant in her
country with outsiders on the grounds that they would be used to manufacture
patented products that would benefit foreign companies, and the products they
produced would be unaffordable to Indonesians. Supari contended the H5N1 virus
was made by the CIA with the intention of afflicting the Islamic world and
bringing financial instability to countries that were compelled to buy U.S.
products. She created the notion that a virus found first in any given country
was the sovereign possession of that nation.

Supari’s contentions spawned a long, difficult period of
negotiations that ultimately led to the2011 PIP,
the WHO’s Pandemic Influenza Preparedness (PIP) Framework. The PIP augments the
International Health Regulations, creating a series of understandings that are
flu-specific regarding sample sharing, patents, and profits from products
derived from viral discovery. Chan's tough response to Memish’s accusations
no doubt stems from her concern that the Saudis could invoke provisions of the
flu-specific PIP, demanding control over the MERS-nCoV samples, patents, and
products.

I will leave detailed analysis to great legal experts
familiar with the IHR, WTO, TRIPS, PIM, and other alphabet soup of trade and
patent fights. The best in my book comes from David Fidler of the University of
Indiana, who shared his
viewswith Canadian
media this week.

Meanwhile, the virus is spreading – somehow
– from an unknown reservoir host to people in the Middle East. While
fame-grabbing scientists, shame-averse Saudis and possible patent-pawing
product developers compete, Nature is doing its thing.

This is simply disgusting.

This is the final essay in my
series related to the sixty-sixth session of the World Health Assembly.

Nations that have confirmed cases of MERS-CoV to date:

Jordan

Qatar

Saudi Arabia

United Arab Emirates (UAE)

France

Germany

Tunisia

United Kingdom

UPDATE TO ABOVE BLOG, ADDED MAY 27, 2013

MARGARET CHAN GAVE BRIEF CLOSING REMARKS TO THE ASSEMBLY, PRIMARILY FOCUSED ON THE MERS CoV SITUATION. Key elements of her speech are:

"Ladies and gentlemen,

Transparency and solidarity. These are words I
heard repeatedly during the session, and especially during discussion of the
item on the International Health Regulations.

Looking at the overall
world health situation, my greatest concern right now is the novel
coronavirus.

We understand too little about this virus when viewed
against the magnitude of its potential threat. Any new disease that is emerging
faster than our understanding is never under control.

We do not know
where the virus hides in nature. We do not know how people are getting infected.
Until we answer these question, we are empty-handed when it comes to
prevention.

These are alarm bells. And we must respond.

The
novel coronavirus is not a problem that any single affected country can keep to
itself or manage all by itself. The novel coronavirus is a threat to the entire
world. As the Chair of committee A succinctly stated: this virus is something
that can kill us.

Through WHO and the IHR, we need to bring together the
assets of the entire world in order to adequately address this
threat.

We need more information, and we need it quickly,
urgently.

As I have announced, joint WHO missions with the Kingdom of
Saudi Arabia and Tunisia will take place just as soon as possible. The purpose
is to gather all the facts needed to conduct a proper risk assessment.

I
thank Member States for supporting my views on the seriousness of this
situation."